PRDM16 Inhibits Cell Proliferation and Migration via Epithelial-to-Mesenchymal Transition by Directly Targeting Pyruvate Carboxylase in Papillary Thyroid Cancer

Wan-Lin Liu; Wan-Lin Liu; Qing Guan; Qing Guan; Duo Wen; Duo Wen; Ben Ma; Ben Ma; Wei-Bo Xu; Wei-Bo Xu; Jia-Qian Hu; Jia-Qian Hu; Wen-Jun Wei; Wen-Jun Wei; Duan-Shu Li; Duan-Shu Li; Yu Wang; Yu Wang; Jun Xiang; Jun Xiang; Tian Liao; Tian Liao; Qing-Hai Ji; Qing-Hai Ji

doi:10.3389/fcell.2021.723777

Frontiers in Cell and Developmental Biology (Nov 2021)

PRDM16 Inhibits Cell Proliferation and Migration via Epithelial-to-Mesenchymal Transition by Directly Targeting Pyruvate Carboxylase in Papillary Thyroid Cancer

Wan-Lin Liu,
Wan-Lin Liu,
Qing Guan,
Qing Guan,
Duo Wen,
Duo Wen,
Ben Ma,
Ben Ma,
Wei-Bo Xu,
Wei-Bo Xu,
Jia-Qian Hu,
Jia-Qian Hu,
Wen-Jun Wei,
Wen-Jun Wei,
Duan-Shu Li,
Duan-Shu Li,
Yu Wang,
Yu Wang,
Jun Xiang,
Jun Xiang,
Tian Liao,
Tian Liao,
Qing-Hai Ji,
Qing-Hai Ji

Affiliations

Wan-Lin Liu: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Wan-Lin Liu: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Qing Guan: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Qing Guan: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Duo Wen: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Duo Wen: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Ben Ma: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Ben Ma: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Wei-Bo Xu: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Wei-Bo Xu: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Jia-Qian Hu: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Jia-Qian Hu: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Wen-Jun Wei: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Wen-Jun Wei: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Duan-Shu Li: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Duan-Shu Li: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Yu Wang: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Yu Wang: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Jun Xiang: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Jun Xiang: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Tian Liao: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Tian Liao: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Qing-Hai Ji: Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
Qing-Hai Ji: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

DOI: https://doi.org/10.3389/fcell.2021.723777
Journal volume & issue: Vol. 9

Abstract

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PRDM16 (known as MEL1), a member of the PR domain zinc finger family, has been implicated in multiple biological processes, including cancers. It is not clear yet whether PRDM16 is involved in tumor progress of papillary thyroid cancer (PTC). We identified the PRDM16 expression level in PTC tissues by qRT-PCR and analyzed its relationship with clinical characteristics in both Fudan University Shanghai Cancer Center (FUSCC) and TCGA cohorts. We tested the function of PRDM16 in PTC cells both in vivo and in vitro. We found a direct downstream target of PRDM16, pyruvate carboxylase (PC), by RNA-sequencing, rescue experiments, luciferase assay, and chromatin immunoprecipitation assay. PRDM16 was downregulated in papillary thyroid cancer tissues and was significantly related with lymph node metastases and extrathyroidal extension in both FUSCC and TCGA cohorts. Overexpression of PRDM16 could attenuate proliferation and migration of PTC cells via inhibiting the epithelial-to-mesenchymal transition process. PC was upregulated in papillary thyroid cancer tissues. Knockdown of PC could inhibit proliferation and migration in TPC-1 and K1 cells. The repression effect on cell proliferation and migration from PRDM16 was PC dependent. PRDM16 could directly bind to the PC promoter and inhibit its expression at the transcription level. Moreover, the mRNA expression level of PRDM16 and PC was negatively related in human PTC tissues. In conclusion, PRDM16 exhibited an antitumor effect and EMT inhibition function in PTC by directly binding with the PC promoter. PRDM16 may be a novel therapeutic target in papillary thyroid cancer.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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